Process for acylation



. reaction medium.

Patented Aug. 15,

UNITED STATES {PATEN OFFICE PROCESS FOR ACYLATION Virgil L. Hanslcy, Niagara Falls, N. Y., assignorto E. I. du Pont lie Ncmours & Company, Wilmington, Del., a corporation of Delaware No Drawing.

application April 19, 194i,

o ilinai Serial No. 389,360. Divided and this application August 20, 1943, Serial No. 499,382

I 9Claims- This invention relates to a process forthe acylation of organic compounds and particularly to a process for the acylation of certain secondary alcohols which utilizes vinyl esters as acylating agents.

This application is a 1941; now Patent No. 2,342,613.

The prior art discloses no method for utilizing vinyl esters as .acylating agents in the acylation,

the present invention is concerned.

One of the objects of this invention is to provide a new and improved method for the acylation of certain secondary alcohols. Another ob- Ject is to provide a practical and economical method for the acylation of these secondary alof the substituted secondary alcohols with which division of my copending application, Serial Number 389,360, filed April 10,

zoo-491 v metal salt be utilized to maintain thepH of the reaction medium somewhat above-7.0 in order .to obtain appreciable quantities of the desired ester by the process of my invention. I prefer to maintain-a pH of 7.5 to 9.0, since I have found that in general the best results are obtained within this range.

However, the pH of the reaction medium may be maintained above 9.0 by means of the alkali metalsalt catalyst with satisfactory results, and in certain cases, for example, such procedure may be desirable when utilizing secondary alcohols which react comparatively slowly with the vinyl ester. I

The rate of reaction may be controlled by the rate of addition of the alkali metal salt catalyst or one of the reactants and cooling or heating cohols by which good yields of the desired ester may be obtained. A further-object is to provide a methodfor the acylation of certain secondary alcohols which is simple/to operate and which may be carried out at comparatively low temperatures in easily obtainable equipment These and other objects will be apparent from the ensuing description of my invention.

The above objects are attained in accordance with my invention by reacting a vinyl ester with certain secondary alcohols in the presence of certain alkali metal salts which are sufliciently al-" kaline to maintain a pH greater than 7.0 in the I have'found that when a vinyl ester, for ex- .ample vinyl acetate,-is added to certain secondary alcohols in the presence of such alkali metal salts the reactlon'is smooth, rapid, and substantially complete and the desired ester is readily obtained in good yield. i

The alkali metal salts which I have found effective as catalysts for the reaction between the secondary alcohols and vinyl esters are the alkali metal cyanides, silicates, carbonates; and tetraborates, for example, sodium cyanide, potassium cyanide, sodium silicate, sodiumcarbonate, and

the reaction mixture. While the reaction with some secondary alcohols is rapid and strongly exothermic, with others the reactionis slower and in some instances a longer time or higher temperature or a combination of these conditions may be utilized to insure complete-reaction. For

. soluble to produce satisfactory results in any desodium tetraborate. I have discovered that when one of these salts or mixtures of two or more of these salts are added to a mixture containing a vinyl ester and certain secondary alcohols in sired acylation. In general, I prefer to add nhydrous catalysts to the reactants, since the pl%sence of water tends to cause loss of the desi ed product by hydrolysis; However, hydrated salts or salts containing small amounts of free moisture are operable in the process of my invention.

Myprocess may be carried out at any desired temperature compatible with the particular reactants used and the product obtained. Generalamounts suilicient to maintain a pH greater than a 7,0, good yields of the desired ester are obtained.

when the pH of the reaction medium is maintained considerably above 7.0, for instance 8.0 to

9.0 or higher, the reaction may be very rapid and in some cases, violent. At a pH of 7.0 or lower, little or no reaction occurs .and I have discovered 1y I have found it desirable to operate my process at about room temperature and in some cases as high as 'C. to C. In some instances it may be preferable to reflux the reaction mixture. to insure complete reaction.

I am aware of the fact that it has been proposed to utilize acid catalysts for the 'acylation of priniary alcohols but I have. found that acidic catathat it is essential that sufficient of the alkali 55 Ms are ineiiective for the acylation of the subof halo-methyl,

methyl, hydroxy-methyl, alkoxy-methyl, aryloxymy invention:

. dissolved potassium cyanide was reaction system consisting of a coil of inch stituted secondary alcohols with which the present invention is concerned. I

, The secondary alcohols whichare within the scope of my invention are those compounds represented by the formula wherein R2 is selected from the group consisting cyano, cyano-methyl, aldomethyl, acyloxy-methyl, ester, and 2-oxy-2 cyanoethyl radicals, and R1 is selected from the group consisting of alkyl, aryl, hydro-aromatic, 'hydroxy-alkyl,.and radicals identical with R2.

Throughout the claims the substituent .radicals of the secondary alcoholic compounds which are operable in the process of my invention are defined as follows: halo-methyl designates the radicals, -CHzX in which X may be chlorine, bromine, or iodine; the cyano radical, CN; cyanomethyl, CHzCN; hydroxy-methyl, CH2OH; ester, COOY- and acyloxy-methyl, -'-CHz0O CY,

in which Y is an alkyl or aryl radical; aldotillation of a 510 gm. aliquot of the reaction mixin which Z i an oxy radical; and hydro-aromatic is a cyclo-paraflin radical such as cyclo-hexyl.

illustrative of the secondary alcohols which I 'have observed to acylate readily in accordance with the process of my invention are methyl lactate, aldol,- glycerol, diacetin, aldol cyanhydrin,

lactonitrile, and glycerol alpha-gamma-dichloro-- 'hydrin. Compounds such as aceto-acetic ester and beta-cyano beta -acetoxyethyl methyl carbinol are also operative in the process of my invention.

The following procedure illustrates a satisfactory method of carrying out the process of my invention. The secondary alcohol to be acylated is placed in a suitable reaction vessel. For carrying out the process on' a small scale a threenecked flask equipped with a stirrer and inlet .for vinyl ester may conveniently be .used. The

reaction flask is immersed in a bath arranged for heating or cooling and sufficient alkali metal saltcatalyst is added to the compound to beacylated to maintain an alkaline reaction medium. The viny lester is added gradually to the contents of the flask while the reaction mixture is agitated. The rate of addition of vinyl ester and the rate oi cooling or heating are adjusted so .as to maintainthe desired reaction temperature. The reaction .in most instances is rapid and is substantially complete by thetime the vinyl. ester has been added, When the reaction is completed the product may be isolated by distillation. The alkali may be neutralized before distillation to avoid hydrolysis.

-'I 'he following examples illustrate the process of Example 1 Methyl lactate, 546 gms., containing 5 grms. of

charged into a the reaction mixture was made to flow from the reservoir thru the coil and pump and back to the reservoir again thus providing both cooling and agitation. Vinyl acetate, 453 gms; was introduced slowly over a period of 0.5 hr. The heat generated'by the reaction was, removed practically at once by the cooling bath so that the temperature of the reactants never was over 29 C. Methyl lactate acetate, B. P. 40-50 C. at 2 mm. was obtained in yield.

Example 2 of 20-25 C. The reaction product was rectified immediately thereafter at atmospheric pressure. A yield of 87.5% of-lactonitrile acetate, B. P. C., was obtained.

Example 3 The circulation system described in Example 2 charged with 500 gms. of aldol containing 5 gms. of dissolved potassium cyanide was treated at 20-25" C. with 488 gms. of vinyl acetate. The disture gave 320 gms. or an 86.5% yield of aldol acetate, B. P. 70-85" C. at 2-3 mm.

Comparable results are obtained when sodium cyanide, sodium silicate, sodium carbonate, orv sodium tetraborate is substituted for the potassium cyanide catalyst in the foregoing examples.

In general I prefer to use approximately equi- -molecular proportions of secondary alcohol and vinyl ester, since the reaction is substantially complete and an excess of either reactant is not required. However,- in some instances it may be found. desirable to use an excess ofone of the reactants. For example, such an excess may be utilized as a solvent for the reaction mixture.

Many modifications of my invention may be made without departing from the scope thereof. My process may be carried out as a batch or as a. continuous process. Moreoventhe reaction may be carried out in the presence of solvents inert with respect to the reactants and catalyst employed. Also the products may be recovered by means other than distillation. For example, the acetaldehyde formed may be removed by adding an agent which will react with the acetaldehyde to form a compound capable of being removed by mechanical means. Vinyl esters other than vinyl acetate, for instance vinyl formate, vinyl propionate or vinyl butyrate' may be utilized as the acylating agent. Many other modifications will be apparent to those skilled in the art without departing from the scope of this invention, the essentialfeature of which comprises a process for the acylation of certain secondary alcohols by reacting said alcohols with a vinyl ester in the presence of alkali metal cyanides, silicates, carbonates, or tetraborates, and maintaining an alkaline. reaction medium by means of said alkali metal salts.

The process of my invention is useful in the preparation of a wide variety of esters which may be used as solvents or for the synthesis of other compounds.

The process of my invention possesses many 75 advantages which will be apparent to those skilled in the art. The process is simple and easily operated on any desired scale, high yields of the desired esters are obtained and the product is easily isolated in pure form. Furthermore, the use of an alkali metal salt as a catalyst avoids the necessity for corrosion resistant equipment such as is required by a process which utilizes acidic materials. sides in the fact that the process of my invention may be operated eiiiciently at'comparatively low temperatures thus avoiding undesirable side reactions and consequent loss in yield which occur at high temperatures. The process of my invention is valuable for the preparation of esters of certain secondary alcoholic compounds since no previous method which utilizes vinyl esters for the acylation of these compounds is known.

I claim:

1. The process for the acylation of methy lactate which comprises reacting a vinyl ester with methyl lactate in the presence of'a compound selected from the group consisting of alkali metal cyanides, silicates, carbonates, and tetra-' borates, and maintaining the pH of the reaction mixture above 7.0 by means of said compound.

2. The process which comprises reacting vinyl rormate with methyl lactate in the presence of a compound selected from the group consisting of alkali metal cyanides, silicates, carbonates, and tetraborates, and maintaining the pH of the reaction mixture above 7.0 by means of said compound. I

3. The process which comprises reacting vinyl butyrate with methyl lactate in the presence oi. a compound selected from the group consisting of alkali metal eyanides, silicates, carbonates, and tetraborates, and maintainingthe pH of the reaction mixture above -7.0 by means of said compound.

A further important advantage re- 4. The process for the acylation of methyl lactate which comprises reacting a vinyl ester' with methyl lactatein the presence of potassium cyanide, and maintaining the pH of the reaction mixture above 7.0 by means of said potassium cyanide 5. The process for th acylation of methyl lactate which comprises reacting vinyl acetate with methyl lactate in the presence 0! potassium cyanide, and maintaining the pH of the reaction mixture above 7.0 by means of said potassium cyanide,

6. The process for the acylation of methyl 'lactate which comprises reacting a vinyl ester with methyl lactate in the presence of sodium cyanide,eand maintaining the pH of the reaction mixture above 7.0 by means of said sodium cyanide. V

'1. The process for the acylation of methyl lactate which comprises reacting vinyl acetate with methyl lactate in the presence ofsodium cyanide, andvmaintaining the pH of the reaction mixture above 7.0 by means 0! said sodium cyanide.

8. The process forthe acylation oi. methyl: vlactate wh h comprises reacting a vinyl ester with methyl lactate in the presence of sodium silicate, and maintaining the pH of the reaction mixture above 1.0 by means of said sodium silicate.

9. The process for the acylation of methyl lactate which comprises reacting vinyl acetate with methyl lactate in the presence of sodium silicate, and maintaining the pH of the reaction mixture above 7.0 by meansof said sodium VIRGIL L. HANSLEY. 

